Center for Translational Cancer Nanomedicine

拟议的中心的目的是提供快速翻译我们的实验室研究的一个广泛的纳米药物癌症与深入的物理化学，体内处置和成像研究到一个真实的工业产品，通过开发适当的技术和扩大规模的生产试验批次的候选人的临床前和临床评价GMP/GLP条件。我们将在波士顿东北大学（NU）建立一个癌症纳米技术卓越中心（CCNE），与贝斯以色列女执事医院、哈佛医学院、罗格斯大学、新泽西州立大学、奥本大学和Nemucore Medical Innovations，Inc.合作。拟议的CCNE将与NIH指定的新泽西癌症研究所和SPORE合作。CCNE将利用基于NU的高速纳米制造中心（NSF资助的纳米科学与工程中心）的支持和设施。 跨学科合作将使基础生物学知识库与物理科学和工程方法相结合，密切参与规模扩大和生产，迅速将实验室研究转化为动物试验和GMP生产，并缩小抗癌疗法发现和开发之间的差距。CCNE将专注于多功能靶向设备，这些设备将绕过当前的生物屏障，以适当的时机将多种治疗剂以高局部浓度直接输送到癌细胞。该中心的主要目标将是开发、临床前体外和体内测试、表征、放大和在GMP条件下生产最有前途的癌症纳米制剂测试批次。纳米载体将包括聚合物胶束、脂质体、聚合物颗粒和树枝状聚合物，而待使用的药物将包括促凋亡剂、DNA和siRNA以及诊断标记。拟议的全国核心网将：a）创建并提供适当的“起始材料”; B）通过体外研究建立概念验证; c）使用动物模型进行药理学研究; d）进行各种体内模型研究; e）提供质量保证;以及f）为用于癌症治疗和诊断的广泛纳米制剂开发生产方案。 公共卫生相关性：我们希望这个模型程序将避免与零碎的基础研究相关的问题，许多独立调查的发展努力。该中心的组织是为了在GMP/GLP条件下快速扩大和开发在实验室中显示为有效的抗肿瘤药物。该中心将提供及时、有意义的临床试验所需的候选药物的质量和数量。

The proposed Center is designed to provide rapid translation of our bench studies of a broad set of nanomedicines for cancer with in-depth physico-chemical, in vivo disposition and imaging studies into a real industrial product by developing the appropriate technologies and scaling them up for manufacture of test batches of candidates for preclinical and clinical evaluation under GMP/GLP conditions. We will establish a Center for Cancer Nanotechnology Excellence (CCNE) at Northeastern University (NU), Boston with collaborations at Beth Israel Deaconess Hospital; Harvard Medical School; Rutgers, The State University of New Jersey, Auburn University, and Nemucore Medical Innovations, Inc. The proposed CCNE will collaborate with the NIH-designated Cancer Institute of New Jersey and SPORE. The CCNE will utilize the support and facilities of the NU-based Center for High-rate Nanomanufacturing (NSF-funded Nanoscale Science and Engineering Center). Cross-disciplinary collaboration will enable integration of the fundamental biological knowledge base with physical science and engineering approaches for intimate involvement in scale-up and manufacture to rapidly translate bench research into animal testing and GMP production and to narrow the gap between discovery and development of anticancer therapeutics. The CCNE will concentrate on multifunctional, targeted devices that will bypass current biological barriers to delivery of multiple therapeutic agents at high local concentrations, with appropriate timing, directly to cancer cells. The main objective of the Center will be to develop, test pre-clinically in vitro and in vivo, characterize, scale up and manufacture under GMP conditions test batches of the most promising nanopreparations for cancer. Nanocarriers will include polymeric micelles, liposomes, polymeric particles, and dendrimers, while the drugs to be used will include pro-apoptotic agents, DNA, and siRNA together with diagnostic labels. The proposed CCNE will: a) create and supply appropriate "starting materials"; b) establish proof-of-concept through in vitro studies; c) conduct pharmacologic studies with animal models; d) perform a variety of in vivo model studies; e) provide quality assurance; and f) develop production schemes for a broad set of nanopreparations for cancer treatment and diagnosis. Public Health Relevance: We expect this model program will avoid the problems associated with piece-meal basic research, development efforts by many independent investigations. The Center is organized for the rapid scale-up and development, under GMP/GLP conditions, of the drugs shown in the lab to be effective anti-tumor agents. The Center will provide the quality and quantity of drug candidates necessary for prompt, meaningful clinical trials.